Response to therapy: modified intent-to-treat population
| Parameters | Insulin glargine with or without metformin plus | ||
|---|---|---|---|
| Lixisenatide 20 µg once daily (n = 297) | Insulin glulisine once daily (n = 298) | Insulin glulisine thrice daily (n = 295) | |
| FPG, mmol/L (mg/dL); n | |||
| Baseline, mean ± SD | 6.6 ± 1.8 (119 ± 33); 295 | 6.9 ± 2.0 (123 ± 36); 295 | 6.7 ± 1.9 (120 ± 34); 294 |
| Week 26 LOCF, mean ± SD | 6.6 ± 2.0 (119 ± 35); 295 | 6.7 ± 1.9 (120 ± 35); 295 | 6.7 ± 2.0 (121 ± 36); 294 |
| LS mean change ± SE | −0.2 ± 0.1 (–4 ± 3); 295 | −0.2 ± 0.1 (–4 ± 3); 295 | −0.1 ± 0.1 (–1 ± 3); 294 |
| LS mean (95% CI) treatment difference | – | −0.0 (–0.32, 0.30) | −0.2 (–0.48, 0.14) |
| (–0.2 [–5.7, 5.4]) | (–3.0 [–8.6, 2.6]) | ||
| 2-h PPG, mmol/L (mg/dL);* n/N | |||
| Baseline, mean ± SD | 14.1 ± 3.6 (254 ± 65); 69/90 | 13.8 ± 3.5 (249 ± 63); 55/88 | 14.6 ± 3.5 (262 ± 63); 68/295 |
| Week 26 LOCF, mean ± SD | 10.2 ± 3.9 (184 ± 70); 69/90 | 12.2 ± 3.4 (220 ± 60); 55/88 | 12.7 ± 3.9 (229 ± 69); 68/295 |
| LS mean change ± SE | −3.6 ± 0.6 | −1.6 ± 0.6 | −1.4 ± 0.6 |
| (–66 ± 11); 69/90 | (–28 ± 11); 55/88 | (–25 ± 11); 68/295 | |
| LS mean (95% CI) treatment difference | – | −2.1 (–3.3, –0.8) | −2.2 (–3.4, –1.1) |
| (–37.3 [–59.2, –15.3]) | (–40.2 [–61.1, –19.2]) | ||
| HbA1c, % (mmol/mol); n | |||
| Baseline after 12-week run-in optimization, mean ± SD | 7.8 ± 0.6 (62 ± 6.6); 292 | 7.7 ± 0.6 (61 ± 6.6); 292 | 7.8 ± 0.6 (62 ± 6.6); 295 |
| Week 26 LOCF, mean ± SD | 7.2 ± 0.8 (55 ± 8.7); 292 | 7.2 ± 0.8 (55 ± 8.7); 292 | 7.0 ± 0.7 (53 ± 7.7); 295 |
| LS mean change ± SE | −0.6 ± 0.1 (–6.6 ± 1.1); 292 | −0.6 ± 0.1 (–6.6 ± 1.1); 292 | −0.8 ± 0.1 (–8.7 ± 1.1); 295 |
| LS mean (95% CI) treatment difference | – | −0.1 (–0.17, 0.06) | 0.2 (0.10, 0.33) |
| (–0.5 [–1.9, 0.7]) | (2.3 [1.0, 3.5]) | ||
| HbA1c <7% at week 26† | |||
| n/N (%) | 123/292 (42.1) | 112/292 (38.4) | 145/295 (49.2) |
| Treatment difference, % (95% CI) | – | 3.7 (–4.03, 11.49) | −7.3 (–15.07, 0.56) |
| HbA1c ≤6.5% at week 26† | |||
| n/N (%) | 60/292 (20.5) | 52/292 (17.8) | 91/295 (30.8) |
| Treatment difference, % (95% CI) | – | 2.7 (–3.59, 9.01) | −10.5 (–17.33, –3.59) |
| Body weight, kg; n | |||
| Baseline, mean ± SD | 90.1 ± 17.4; 295 | 88.4 ± 15.9; 295 | 90.0 ± 17.2; 295 |
| Week 26 LOCF, mean ± SD | 89.4 ± 18.1; 295 | 89.3 ± 16.3; 295 | 91.3 ± 17.3; 295 |
| LS mean change ± SE | −0.6 ± 0.3; 295 | 1.0 ± 0.3; 295 | 1.4 ± 0.3; 295 |
| LS mean (95% CI) treatment difference | – | −1.7 (–2.26, –1.06) | −2.0 (–2.59, –1.40)§ |
| Patients with no weight gain;†‡ n/N (%) | 191/295 (64.7) | 108/295 (36.6) | 90/295 (30.5) |
| Weighted average response rate | |||
| (95% CI) treatment difference (%) | – | 28.1 (20.5, 35.8) | 34.2 (26.7, 41.7) |
| Insulin glargine dose, U/day; n | |||
| Baseline, mean ± SD | 67 ± 32; 292 | 65 ± 32; 294 | 65 ± 27; 294 |
| Week 26 LOCF, mean ± SD | 67 ± 36; 292 | 64 ± 36; 294 | 61 ± 29; 294 |
| LS mean change ± SE from baseline to week 26 | 0.7 ± 1.0; 292 | −0.1 ± 1.0; 294 | −3.1 ± 1.0; 294 |
| LS mean (95% CI) treatment difference | – | 0.8 (–1.41, 2.92) | 3.8 (1.66, 6.00) |
| Daily insulin glulisine dose, units; n | – | ||
| Week 26 LOCF, mean ± SD | 10 ± 8; 295 | 20 ± 13; 293 | |
| Total daily insulin dose (glargine + glulisine), units; n | |||
| Week 26 LOCF, mean ± SD | 67 ± 32; 292 | 74 ± 39; 295 | 81 ± 34; 294 |
| Exploratory analyses | |||
| Patients with ≥2% weight loss;† n (%) | 97 (32.9) | 33 (11.2) | 32 (10.8) |
| Weighted average response rate treatment difference, % (95% CI) | – | 21.7 (15.27, 28.11) | 22.0 (15.61, 28.43) |
| Patients with ≥3% weight loss;† n (%) | 69 (23.4) | 21 (7.1) | 18 (6.1) |
| Weighted average response rate treatment difference, % (95% CI) | – | 16.3 (10.69, 21.97) | 17.3 (11.75, 22.85) |
| Patients with ≥5% weight loss;† n (%) | 36 (12.2) | 11 (3.7) | 7 (2.4) |
| Weighted average response rate treatment difference, % (95% CI) | – | 8.5 (4.13, 12.86) | 9.8 (5.69, 13.98) |
Summary statistics (mean ± SD) for HbA1c, FPG, 2-h PPG, and body weight were based on modified intent-to-treat population; all available data were included in the analysis. An ANCOVA model was used for calculation of LS mean treatment difference for HbA1c, FPG, 2-h PPG, and body weight, with treatment groups, week – 1 strata of HbA1c (<8 or ≥8% [<64 or ≥64 mmol/mol]), metformin use (yes or no) strata at randomization, and country as fixed effects, and the corresponding baseline value as a covariate. Patients with both baseline and week 26 (LOCF) measurements are included. LOCF, last observation carried forward.
↵*After a standardized meal in patients administered treatment before breakfast.
↵†Weighted average of proportion difference between treatment groups from each strata (week – 1 strata of HbA1c [<8.0 or ≥8.0%], randomization strata of metformin use) using Cochran–Mantel–Haenszel weights.
↵‡Prespecified end point.
↵§P < 0.0001.